alzheimer's: upsetting the balance

​Alzheimer’s: Upsetting the Balance The previous article, drawing heavily on Dr. Dale Bredesen’s The End of Alzheimer’s, suggested Alzheimer’s is the brain’s response to three threats – inflammation; shortage of nutrients, hormones, and other molecular support; and toxicity – and then suggested some general strategies for addressing these issues.

Brain health involves building and maintaining neurons and synapses (connections between neurons), and also destroying old neurons and unused synapses. Construction (memory of the important) and destruction (forgetting of the unimportant) are equal parts of the equation for a healthy brain. Balance - so much in our world (and health) is about balance.

“Forgetting” is normal in some cases. We have all experienced learning something (capitals of the states, e.g.), not using that information, and then having a recollection of only some of the information decades later. Connections to stored unused memories are often lost in favor of new connections for new information. Diseases of cognitive decline, including Alzheimer’s, however, are characterized by a higher rate of synapse destruction than construction, a downsizing of the brain. Remembering that the body never does anything wrong, we must look at why the brain is downsizing in order to reverse its direction.

There is nothing wrong with holding on to all information, but if resources are insufficient, information that is not critical to life is better deleted than information critical to life. In Alzheimer’s the “last hired, first fired” applies to memories. Perhaps that is fortunate, since remembering how to breathe or speak is more important than what you saw on TV last night. Life skills are preserved while new memories are not formed.

Conventional treatment has been based on eliminating the amyloid-beta plaque. A picture is beginning to develop of what this plaque does, and it is not all bad, so we need to see where amyloid originates. Amyloid Precursor Protein (APP) is produced by the neurons, and there is a protease (an enzyme that breaks down protein peptide bonds) that acts like a pair of scissors cutting the APP at either one or three places.

When one cut is made, the two fragments maintain synaptic connections, assist neuron growth, and block the neuron’s suicide program.

When three cuts are made, one of the four peptides created is amyloid-beta, but all 4 play roles in the loss of synapses and the activation of the neuron’s suicide program, resulting in brain atrophy.

This information makes it clear that we need to optimize the production of the peptide in #1 above and minimize the production of the peptide in #2. And we also see that people with Alzheimer’s have peptide #2 dominant.

It is not so much about preventing amyloid-beta or removing this plaque, but what do we do to encourage #1 and discourage #2. “For decades, Alzheimer’s researchers have pursued the idea that clearing out clumps of a protein called amyloid would delay or cure the brain disease. But in hundred-million-dollar trial after hundred-million-dollar trial, the approach hasn’t panned out. In an editorial last week in the New England Journal of Medicine, Alzheimer’s researcher M. Paul Murphy of the University of Kentucky declared the impending death of this so-called amyloid hypothesis.” (NPR)

Like cholesterol or inflammation, the body is making amyloid for a reason. Removing cholesterol or inflammation or amyloid without removing the cause does not restore health. Dr. Bredesen’s theory and treatment of Alzheimer’s is based on finding “36 holes in the roof,” that is, 36 contributors to whether the brain builds or downsizes.

In CardioVascular Disease, addressing the factors causing arterial plaque reverse CVD. Addressing every factor is not necessary to slow the process, but the more favorable changes that are made, the better the result. The cholesterol is simply present, so reducing cholesterol has not led to better outcomes. Effective treatment requires addressing causes. So it is with Alzheimer’s 36 holes – addressing more causes leads to better results. In fact, this is why drugs have had such a dismal record, because they address only one or perhaps a few issues, at most.

Considering the large number of factors contributing to Alzheimer’s, a strategy for reversing Alzheimer’s must be specific to the individual. The focus must be on the areas in which the individual is out of balance. You may want to know whether you have zero, one, or two copies of the ApoE4 gene, since these are related to a 9%, 30%, or greater than 50% probability of having Alzheimer’s. That is a good starting point based on the increasing probability of Alzheimer’s with one or two copies of this gene. Or you may decide that knowing the probability is not that important, because the steps to improving memory and overall brain health are exactly the same steps as improving overall body health. This need for balance in body systems is not unique to the brain.

For a quick comparison, look at osteoporosis. Bone destruction is moving faster than bone remodeling/construction. Old bone becomes brittle and must be removed, and new stronger bone replaces it. If there is insufficient raw material for new bone, a deficit (osteopenia progressing to osteoporosis) develops. A drug that slows bone destruction (bisphosphonates such as Fosomax) results in the accumulation of older, brittle bone rather than encouraging new bone growth, appearing stronger but in fact more easily subject to fractures. The body eventually recognizes old bone is not being destroyed and quits making new bone. We are not addressing causes.

There once was a margarine commercial that stated “It’s not nice to fool Mother Nature.” No, margarine did not fool Mother Nature, and the lesson we relearn time and again is that you cannot fool Mother Nature. The nature of the body is complex and unique to each individual. There are some guidelines on maintaining health, on giving the body what it needs to avoid diseases, including CVD, osteoporosis and Alzheimer’s. We will look at those in the next article.​​Note:This article, like all others in these e-newsletters and website, is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This is not a substitute for medical advice. ​If you have a health condition requiring treatment, please consult a healthcare professional.